762PD - Impact of enzalutamide on skeletal related events (SREs), pain and quality of life (QoL) in the PREVAIL trial

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Presenter Yohann Loriot
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors Y. Loriot1, K. Miller2, C.N. Sternberg3, K. Fizazi4, J.S. De Bono5, S. Chowdhury6, C. Higano7, S. Noonberg8, S. Holmstrom9, H. Mansbach10, F.G. Perabo11, D. Phung12, C. Ivanescu13, K. Skaltsa14, T. Beer15, B. Tombal16
  • 1Department Of Cancer Medicine, Institut Gustave Roussey, University of Paris Sud, 94805 - Villejuif/FR
  • 2Department Of Urology, Charite, Campus Benjamin Franklin Medizinische Klinik III, 12200 - Berlin/DE
  • 3Medical Oncology, San Camillo Forlanini HospitalDepartment of Medical Oncology, 152 - Roma/IT
  • 4Department Of Cancer Medicine, Institut Gustave Roussy, University of Paris, Villejuif/FR
  • 5Oncology, Royal Marsden Hospital NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 6Department Of Medical Oncology, Guy's and St. Thomas' Hospital NHS Trust, SE1 9RT - London/GB
  • 7Department Of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, 98109 - Seattle/US
  • 8Clinical Development, Medivation, Inc., San Francisco/US
  • 9Heor, Astellas Pharma Global Development, Leiden/NL
  • 10Medical Affairs, Medivation, San Francisco/US
  • 11Medical Science, Astellas Pharma Global Development, US-60015 - Deerfield/US
  • 12Global Development, Astellas Pharma, Northbrook/US
  • 13Consulting, Quintiles, Hoofddorp/NL
  • 14Consulting, Quintiles, Barcelona/ES
  • 15Ohsu Knight Cancer Institute, Oregon Health & Science University, Portland/US
  • 16Division Of Urology, Cliniques Universitaires Saint-Luc, 1200 - Brussels/BE

Abstract

Aim

Enzalutamide (ENZ) improved overall survival vs. placebo (PL) in PREVAIL, a phase 3 trial in asymptomatic/mildly symptomatic chemotherapy-naïve patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) [Beer et al, ASCO GU 2014]. PREVAIL also prospectively evaluated SREs, pain and QoL.

Methods

Pts were randomized to ENZ (160mg/day; n = 872) or PL (n = 845). SREs were assessed throughout the study and time to 1st SRE measured. QoL was assessed at baseline (BL) and during treatment (tx) on the FACT-P and EQ-5D; changes from BL over time were compared using repeated measures analyses. Pain was assessed with the BPI-SF at BL, and months (mo) 3 and 6. Pts with BL and ≥1 post-BL score were analyzed using pre-specified criteria for clinically meaningful pain progression (pain severity: increase ≥30% from BL; pain interference: increase ≥50% of BL standard deviation) and QoL deterioration (Cella et al, VIH 2009; Pickard et al, HQOL 2007).

Results

Median tx duration was 16.6 (ENZ) and 4.6 (PL) mo; BL pain and QoL scores were similar between arms. Overall, 32% (ENZ) and 37% (PL) of pts reported at least one SRE. Compared to PL, ENZ significantly reduces the risk of 1st SRE occurrence (hazard ratio: 0.72 [0.61, 0.84], p < 0.0001) and Qol deterioration (table). During the first 15 mo of tx, QoL as measured by FACT-P total scores and subscores was significantly better with ENZ (all p < 0.001 vs PL). ENZ significantly improved pain outcomes vs PL during the first 6 months of the tx (table).

Time to 1st deterioration (mo), median (95% Cl)
ENZ (n = 872) PL (n = 845) P-value Hazard ratioa (95% CI)
EQ-5D instrument
Visual analogue scale 22.14 (19.35;27.66) 13.83 (11.07;16.59) <0.001b 0.67 (0.56;0.80)
FACT-P instrument
Physical well-being 10.84 (8.31;11.07) 5.55 (5.49;5.62) <0.001b 0.74 (0.65;0.85)
Functional well-being 8.54 (8.31;11.07) 3.09 (2.86;5.55) <0.001b 0.72 (0.62;0.82)
Emotional well-being 19.48 (16.59;25.07) 11.01 (8.25;11.40) <0.001b 0.67 (0.57;0.79)
Social well-being 24.87 (14.16;NYR) 8.51 (6.01;13.86) <0.001b 0.74 (0.63;0.86)
Prostate Cancer Subscale 5.65 (5.55;8.31) 2.83 (2.79;2.96) <0.001b 0.69 (0.60;0.78)
FACT-P total score 11.30 (11.07;13.86) 5.55 (5.49;5.59) <0.001b 0.62 (0.54;0.72)
Pain progression, n(%)
Pain severity 329/802 (41) 317/628 (50) <0.001c
Pain interference 247/788 (31) 255/613 (42) <0.001c

Conclusions

In PREVAIL, in addition to overall survival benefit, ENZ was also associated with clinically significant patient benefits compared to PL, including a delay in time to 1st SRE, superior QoL, a delay in QoL deterioration, and significantly lower proportion of pts with pain.

Disclosure

Y. Loriot: Consultant/Advisory: Astellas Research Funding: Astellas Other: Sanofi, Janssen, Bayer, Cellgene;

K. Miller: Consulting: Astellas/Medivation Consultancy: Astellas, Amgen, Janssen, Medivation, Novartis, Roche Lectures: Novartis, Janssen, Pierre-Fabre; C.N. Sternberg: Honoraria: Astellas, Johnson & Johnson, Ipsen, Bayer, Millenium; K. Fizazi: Advisory Board: Astellas/Medivation Speaker: Astellas/Medivation; J.S. de Bono: Astellas/Medivation; S. Chowdhury: Advisory Board/Lecture: Astellas, Janssen, Sanofi-Aventis, Dendreon Speaker: GSK; C. Higano: Research funding: Astellas/Medivation, Algeta, Aragon, Dendreon, Sanofi Consultant/Advisory: Astellas/Medivation, Dendreon, Bayer, Johnson & Johnson; S. Noonberg: Employee: Medivation; S. Holmstrom, F.G. Perabo and D. Phung: Employee: Astellas; H. Mansbach: Employee: Medivation; C. Ivanescu: Astellas: payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; K. Skaltsa: Astellas: Payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; T. Beer: Research Funding: Astellas/Medivation, Janssen Consultant: Janssen; B. Tombal: Advisor: Astellas/Medivation, Ferring Speaker: Astellas, Ferring